title: Management of major bleeding complications and emergency surgery in patients on long-term treatment with direct oral anticoagulants, thrombin or factor-Xa inhibitors: proposals of the working group on perioperative haemostasis (GIHP) - March 2013.
abstract: Direct new oral anticoagulants (NOACs) - inhibitors of thrombin or factor Xa - are intended to be used largely in the treatment of venous thromboembolic disease or the prevention of systematic embolism in atrial fibrillation, instead of vitamin K antagonists. Like any anticoagulant treatment, they are associated with spontaneous or provoked haemorrhagic risk. Furthermore, a significant proportion of treated patients are likely to be exposed to emergency surgery or invasive procedures. Given the absence of a specific antidote, the action to be taken in these situations must be defined. The lack of data means that it is only possible to issue proposals rather than recommendations, which will evolve according to accumulated experience. The proposals presented here apply to dabigatran (Pradaxa(®)) and rivaroxaban (Xarelto(®)); data for apixaban and edoxaban are still scarce. For urgent surgery with haemorrhagic risk, the drug plasma concentration should be less or equal to 30ng/mL for dabigatran and rivaroxaban should enable surgery associated with a high bleeding risk. Beyond that, if possible, the intervention should be postponed by monitoring the drug concentration. The course to follow is then defined according to the NOAC and its concentration. If the anticoagulant dosage is not immediately available, worse propositions, based on the usual tests (prothrombin time and activated partial thromboplastin time), are presented. However, these tests do not really assess drug concentration or the risk of bleeding that depends on it. In case of serious bleeding in a critical organ, the effect of anticoagulant therapy should be reduced using a non-specific procoagulant drug as a first-line approach: activated prothrombin complex concentrate (aPCC) (FEIBA(®) 30-50U/kg) or non-activated PCC (50U/kg). In addition, for any other type of severe haemorrhage, the administration of a procoagulant drug, which is potentially thrombogenic in these patients, is discussed according to the NOAC concentration and the possibilities of mechanical haemostasis.
authors.affiliation: Vascular Medicine Department, University Hospital, UJF-Grenoble 1/CNRS TIMC-IMAG UMR 5525/Themas, France. GPernod@chu-grenoble.fr
authors.forename: Gilles
authors.initials: G
authors.lastname: Pernod
authors.forename: Pierre
authors.initials: P
authors.lastname: Albaladejo
authors.forename: Anne
authors.initials: A
authors.lastname: Godier
authors.forename: Charles M
authors.initials: CM
authors.lastname: Samama
authors.forename: Sophie
authors.initials: S
authors.lastname: Susen
authors.forename: Yves
authors.initials: Y
authors.lastname: Gruel
authors.forename: Normand
authors.initials: N
authors.lastname: Blais
authors.forename: Pierre
authors.initials: P
authors.lastname: Fontana
authors.forename: Ariel
authors.initials: A
authors.lastname: Cohen
authors.forename: Juan V
authors.initials: JV
authors.lastname: Llau
authors.forename: Nadia
authors.initials: N
authors.lastname: Rosencher
authors.forename: Jean-François
authors.initials: JF
authors.lastname: Schved
authors.forename: Emmanuel
authors.initials: E
authors.lastname: de Maistre
authors.forename: Meyer M
authors.initials: MM
authors.lastname: Samama
authors.forename: Patrick
authors.initials: P
authors.lastname: Mismetti
authors.forename: Pierre
authors.initials: P
authors.lastname: Sié
mesh_terms: D000284:Administration, Oral; D000925:Anticoagulants / Q000008:administration & dosage / Q000009:adverse effects* / Q000097:blood; D000991:Antithrombins / Q000008:administration & dosage / Q000009:adverse effects* / Q000097:blood; D001562:Benzimidazoles / Q000009:adverse effects; D001777:Blood Coagulation / Q000187:drug effects*; D001780:Blood Coagulation Tests; D003029:Coagulants / Q000009:adverse effects / Q000627:therapeutic use*; D000069604:Dabigatran; D004334:Drug Administration Schedule; D016903:Drug Monitoring / Q000379:methods; D004630:Emergencies; D065427:Factor Xa Inhibitors; D006470:Hemorrhage / Q000139:chemically induced / Q000175:diagnosis / Q000628:therapy*; D006489:Hemostatic Techniques; D006801:Humans; D009025:Morpholines / Q000009:adverse effects; D061214:Patient Safety; D019990:Perioperative Care; D019106:Postoperative Hemorrhage / Q000139:chemically induced / Q000175:diagnosis / Q000628:therapy; D018570:Risk Assessment; D012307:Risk Factors; D000069552:Rivaroxaban; D013514:Surgical Procedures, Operative / Q000009:adverse effects*; D013876:Thiophenes / Q000009:adverse effects; D013997:Time Factors; D016896:Treatment Outcome; D015091:beta-Alanine / Q000009:adverse effects / Q000031:analogs & derivatives
chemical_list: D000925:Anticoagulants; D000991:Antithrombins; D001562:Benzimidazoles; D003029:Coagulants; D065427:Factor Xa Inhibitors; D009025:Morpholines; D013876:Thiophenes; D015091:beta-Alanine; D000069552:Rivaroxaban; D000069604:Dabigatran
keywords: Activated partial thromboplastin time; Activated prothrombin complex concentrate factor VIII inhibitor bypassing activity; Anti-IIa; Anti-Xa; Bleeding; Chirurgie; CkrCl; Creatinine clearance calculated according to the formula of Cockcroft and Gault; FEIBA; GIHP; Hémorragie; NOAC; New oral anticoagulant; PCC; PT; Prothrombin complex concentrate; Prothrombin time; Reversal; Réversion; Surgery; VKA; Vitamin K antagonist; Working Group on Perioperative Haemostasis (Groupe d’Intérêt en Hémostase Périopératoire); aPPT